Journal ArticleDOI
MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts
Thomas Thum,Carina Gross,Jan Fiedler,Thomas Fischer,Stephan Kissler,Markus Bussen,Paolo Galuppo,Steffen Just,Wolfgang Rottbauer,Stefan Frantz,Mirco Castoldi,Jürgen Soutschek,Victor Koteliansky,Andreas Rosenwald,M. Albert Basson,Jonathan D. Licht,John T. R. Pena,Sara H. Rouhanifard,Martina U. Muckenthaler,Thomas Tuschl,Gail R. Martin,Johann Bauersachs,Stefan Engelhardt,Stefan Engelhardt +23 more
TLDR
It is shown that microRNA-21 regulates the ERK–MAP kinase signalling pathway in cardiac fibroblasts, which has impacts on global cardiac structure and function and confirms miR-21 as a disease target in heart failure and establishes the therapeutic efficacy of microRNA therapeutic intervention in a cardiovascular disease setting.Abstract:
MicroRNAs comprise a broad class of small non-coding RNAs that control expression of complementary target messenger RNAs. Dysregulation of microRNAs by several mechanisms has been described in various disease states including cardiac disease. Whereas previous studies of cardiac disease have focused on microRNAs that are primarily expressed in cardiomyocytes, the role of microRNAs expressed in other cell types of the heart is unclear. Here we show that microRNA-21 (miR-21, also known as Mirn21) regulates the ERK-MAP kinase signalling pathway in cardiac fibroblasts, which has impacts on global cardiac structure and function. miR-21 levels are increased selectively in fibroblasts of the failing heart, augmenting ERK-MAP kinase activity through inhibition of sprouty homologue 1 (Spry1). This mechanism regulates fibroblast survival and growth factor secretion, apparently controlling the extent of interstitial fibrosis and cardiac hypertrophy. In vivo silencing of miR-21 by a specific antagomir in a mouse pressure-overload-induced disease model reduces cardiac ERK-MAP kinase activity, inhibits interstitial fibrosis and attenuates cardiac dysfunction. These findings reveal that microRNAs can contribute to myocardial disease by an effect in cardiac fibroblasts. Our results validate miR-21 as a disease target in heart failure and establish the therapeutic efficacy of microRNA therapeutic intervention in a cardiovascular disease setting.read more
Citations
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Crystallin-αB Regulates Skeletal Muscle Homeostasis via Modulation of Argonaute2 Activity
TL;DR: It is established that CryAB is necessary for normal Ago2/RISC activity and cellular homeostasis in skeletal muscle and a novel role of CryAB in the mammalian RNAi/microRNA pathway is highlighted.
Journal ArticleDOI
MicroRNAs in cardiac remodeling and disease.
TL;DR: This review focuses on the recent progress in the understanding of the function of miRNAs in cardiac remodeling and disease, and discusses the diagnostic and therapeutic potential of mi RNAs in heart disease.
Journal ArticleDOI
MicroRNA Involvement in Immune Activation During Heart Failure
TL;DR: The role of inflammatory signaling, TLR4 signaling, IL-1β, TNFα and IL-6 expression appears to coincide with the development of heart failure, and the implication of the renin angiotensin aldosteron system in immunity and heart failure is described.
Journal ArticleDOI
Inhibition of miR-21 alleviated cardiac perivascular fibrosis via repressing EndMT in T1DM
Qianqian Li,Yufeng Yao,Shumei Shi,Mengchen Zhou,Yingchao Zhou,Mengru Wang,Jeng Jiann Chiu,Zhengrong Huang,Weili Zhang,Min Liu,Qing Wang,Qing Wang,Qing Wang,Xin Tu +13 more
TL;DR: The pathway of NF‐κB/miR‐21/SMAD7 regulated the process of EndMT in T1DM, in diabetic cardiomyopathy, which may be regarded as a potential clinical therapeutic target for cardiac perivascular fibrosis.
Journal ArticleDOI
Sp1 mediates microRNA-29c-regulated type I collagen production in renal tubular epithelial cells
Lei Jiang,Yang Zhou,Mingxia Xiong,Li Fang,Ping Wen,Hongdi Cao,Junwei Yang,Chunsun Dai,Weichun He +8 more
TL;DR: It is found that Sp1 was markedly induced and closely correlated with interstitial type I collagen accumulation in kidney tubular epithelia from obstructive nephropathy and miR-29c expression was remarkably reduced in either thetubular epithelial cells from kidney with UUO nePHropathy or TGF-β1-treated NRK-52E cells.
References
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Jan Krützfeldt,Nikolaus Rajewsky,Ravi Braich,Kallanthottathil G. Rajeev,Thomas Tuschl,Muthiah Manoharan,Markus Stoffel +6 more
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Journal ArticleDOI
A microRNA component of the p53 tumour suppressor network
Lin He,Xingyue He,Xingyue He,Lee P. Lim,Elisa de Stanchina,Elisa de Stanchina,Zhenyu Xuan,Yu Liang,Wen Xue,Lars Zender,Jill F. Magnus,Dana Ridzon,Aimee L. Jackson,Peter S. Linsley,Caifu Chen,Scott W. Lowe,Michele A. Cleary,Gregory J. Hannon +17 more
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